Animal models of polyglutamine diseases and therapeutic approaches.
The dominant gain-of-function polyglutamine repeat diseases, in which the initiating mutation is known, allow development of models that recapitulate many aspects of human disease. To the extent that pathology is a consequence of disrupted fundamental cellular activities, one can effectively study strategies to ameliorate or protect against these cellular insults. Model organisms allow one to identify pathways that affect disease onset and progression, to test and screen for pharmacological agents that affect pathogenic processes, and to validate potential targets genetically as well as pharmacologically. Here, we describe polyglutamine repeat diseases that have been modeled in a variety of organisms, including worms, flies, mice, and non-human primates, and discuss examples of how they have broadened the therapeutic landscape.
Marsh
J Lawrence
JL
Developmental Biology Center and the Department of Developmental and Cell Biology, University of California, Irvine, California 92697, USA. jlmarsh@uci.edu
Lukacsovich
Tamas
T
Thompson
Leslie Michels
LM
D000818:Animals; D004195:Disease Models, Animal; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D010455:Peptides / Q000235:genetics* / Q000378:metabolism
D010455:Peptides; C097188:polyglutamine